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The continuing circulation and reassortment with low-pathogenicity avian influenza Gs/Gd (goose/Guangdong/1996)-like avian influenza viruses (AIVs) has caused huge economic losses and raised public health concerns over the zoonotic potential. Virologic surveillance of wild birds has been suggested as part of a global AIV surveillance system. However, underreporting and biased selection of sampling sites has rendered gaining information about the transmission and evolution of highly pathogenic AIV problematic. We explored the use of the Citizen Scientist eBird database to elucidate the dynamic distribution of wild birds in Taiwan and their potential for AIV exchange with domestic poultry. Through the 2-stage analytical framework, we associated nonignorable risk with 10 species of wild birds with100 significant positive results. We generated a risk map, which served as the guide for highly pathogenic AIV surveillance. Our methodologic blueprint has the potential to be incorporated into the global AIV surveillance system of wild birds.

Relationship between pulmonary vein (PV) anatomy and the pathophysiology of paroxysmal atrial fibrillation (PAF) remains incompletely studied. The aim of this study was to determine whether PV anatomy predicts arrhythmogenic PVs. Twenty-six consecutive PAF patients with spontaneous PAF or consistently frequent ectopic beats during electrophysiological study were enrolled. Computed tomography (CT) images for PVs were reconstructed into 3D images. The PV diameter and volume were measured based on the 3D images. The PV myocardial sleeve area was measured based on the 3D voltage mapping results. The PV myocardial sleeve area index was calculated by dividing the sleeve area of each PV by the average sleeve area of all PVs in each patient. The diameter and volume of the arrhythmogenic PVs were larger than those of the non-arrhythmogenic PVs (21.08 ± 4.57 mm vs. 16.47 ± 3.31 mm, P

Tumor recurrence and metastasis are the major causes of death for hepatocellular carcinoma (HCC) patients who are able to receive curative resection. Identifying the predicting biomarkers for tumor recurrence would improve their survival. RNA extracted from fresh frozen tumors and adjacent non-tumor liver tissues of 120 HCC patients were obtained from Taiwan Liver Cancer Network (TLCN) in year 2010 for determination of the carboxypeptidase E (CPE) expression level (including its splicing mutant CPE-ΔN) in the tumor tissue (T) and paired non-tumor liver tissue (N) by real-time quantitative polymerase chain reaction. All patients were male, had chronic hepatitis B virus infection, were in the early pathology stage, and received curative resection. The T/N ratio of the CPE expression level was correlated with the updated survival data from TLCN in 2015. The CPE expression level in the 120 HCC patients was divided into three groups according to the T/N ratio:1, ≥1 and ≤2, and2, respectively. By multivariate analyses, the recurrence-free survival (RFS) was only significantly associated with the pathology stage and the CPE expression level. For overall survival (OS), only the CPE expression level was the significant prognostic factor. The CPE expression level was also significantly correlated with the tumor recurrence for both stage I (p = 0.0106) and stage II patients (p = 0.0006). The CPE mRNA expression level in HCC can be a useful biomarker for predicting tumor recurrence in HCC patients who are in the early pathology stage and able to receive curative resection.

Background The outcome of colon cancer patients without lymph node metastasis is heterogeneous. Searching for new prognostic markers is warranted. Methods One hundred twenty stage I–II colon cancer patients who received complete surgical excision during 1995–2004 were selected for this biomarker study. Immunohistochemical method was used to assess p53, epidermal growth factor receptor, MLH1, and MSH2 status. KRAS mutation was examined by direct sequencing. Results Thirty three patients (27.5%) developed metachronous metastasis during follow up. By multivariate analysis, only female gender (p = 0.03), high serum carcinoembryonic antigen (CEA) level (≧5 ng/ml) (p = 0.04), and MLH1 overexpression (p = 0.003) were associated with the metastasis group. The 5-year-survival rate were also significantly lower for female gender (71.7% versus 88.9%, p = 0.025), high CEA level (64.9% versus 92.4%, p

Goodness-of-fit problem playes a key role in statistical inference because the validity of an assumed model ensures the subsequent inferential rationality.

Introduction: Several Classical Data Examples for Survival Analysis.- Elements of Survival Analysis.- The Cox Proportional Hazards Model.- The AFT, GPH, LT, Frailty, and GLPH Models.- Cross-effect Models of Survival Functions.- The Simple Cross-effect Model.- Goodness-of-Fit for the Cox Model.- Remarks on Computations in Parametric and Semiparametric Estimation.- Cox Model for Degradation and Failure Time Data.- References.- Index.

The proportional hazards (PH) or Cox model holds on E, if the hazard rate has the form $$\begin{aligned} \lambda _{x(\cdot )}(t) = r\{x(t)\} \;\lambda _0(t), \quad x(\cdot ) \in E, \end{aligned}$$ where \(\lambda _0(\cdot )\) is an unspecified baseline hazard rate function , and \(r(\cdot )\) is a positive function on E. The function \(r(\cdot )\) explains the summing effect of all \(x_i(\cdot )\) on the distribution of T.

In this chapter and Chap. 6, we introduce several models which can deal with cross-effect; including the Hsieh model and the simple cross-effect (SCE) model .

Failures of highly reliable units are rare. In order to obtain a complementary reliability information, the accelerated life testing (ALT) is used so that higher level of experimental factors are applied to obtain failures quickly.

The proportional hazards (PH) model was proposed by Sir David Cox just over 40 years ago (Cox 1972). Today, the Cox model is the most important model in survival analysis , reliability and quality of life research, epidemiology, clinical trials , and biomedical studies. There have also been tremendous applications of the Cox model in demography , econometrics , finance, pharmacology, biology, gerontology , insurance, etc. These have marked the great success of the Cox PH model which further induced extended studies of competitive survival regression models and the corresponding development of semiparametric estimation theory, likelihood principle, counting process modeling and applications.

Let \(S_{X}(t)\), \(\lambda _{X}(t)\), and \(\varLambda _{X}(t)\) be the survival, hazard rate, and cumulative hazard functions under a p-dimensional time-dependent covariate X.

It is well known that traditionally the failure time data are used for product reliability estimation or for estimation of survival characteristics. Failures of highly reliable units are rare and other information should be used in addition to censored failure time data. One way of obtaining a complementary reliability information is to use higher levels of experimental factors or covariates (such as temperature, voltage, or pressure) to increase the number of failures and, hence, to obtain reliability information quickly. The accelerated life testing (ALT) of biotechnical systems is a simple practical method for estimation of reliability of new systems without having to wait for the operating lives of them.

Background Familial sick sinus syndrome is associated with gene mutations and dysfunction of ion channels. In contrast, degenerative fibrosis of the sinus node tissue plays an important role in the pathogenesis of acquired sick sinus syndrome. There is a close relationship between transforming growth factor-β1 mediated cardiac fibrosis and acquired arrhythmia. It is of interest to examine whether transforming growth factor-β1 is involved in the pathogenesis of acquired sick sinus syndrome. Methods Overall, 110 patients with acquired SSS and 137 age/gender-matched controls were screened for transforming growth factor-β1 and cardiac sodium channel gene polymorphisms using gene sequencing or restriction fragment length polymorphism methods. An enzyme-linked immunosorbent assay was used to determine the serum level of transforming growth factor-β1. Results Two transforming growth factor-β1 gene polymorphisms (C-509T and T+869C) and one cardiac sodium channel gene polymorphism (H588R) have been identified. The C-dominant CC/CT genotype frequency of T869C was significantly higher in acquired sick sinus syndrome patients than in controls (OR 2.09, 95% CI 1.16–3.75, P = 0.01). Consistently, the level of serum transforming growth factor-β1 was also significantly greater in acquired sick sinus syndrome group than in controls (5.3±3.4 ng/ml vs. 3.7±2.4 ng/ml, P = 0.01). In addition, the CC/CT genotypes showed a higher transforming growth factor-β1 serum level than the TT genotype (4.25 ± 2.50 ng/ml vs. 2.71± 1.76 ng/ml, P = 0.028) in controls. Conclusion Transforming growth factor-β1 T869C polymorphism, correlated with high serum transforming growth factor-β1 levels, is associated with susceptibility to acquired sick sinus syndrome.

Introduction: Recently, two studies revealed that MET amplification was associated with secondary epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance in non-small cell lung cancer (NSCLC) patients. But it remains uncertain whether MET amplification could be related to primary TKI resistance in NSCLC because of limited data. Materials and Methods: MET gene dosage of the tumor tissues from 208 NSCLC patients was investigated by real time quantitative polymerase chain reaction and compared with molecular and clinical features, including EGFR mutations, KRAS mutations, EGFR gene copy numbers, and patient survivals. Three copies were used as the cutoff. Among them, 25 patients were also evaluable for EGFR TKI responsiveness. Results: The proportion of high MET gene dosage was 10.58% (22/208) with higher incidence in squamous cell carcinoma (11.86%) and smokers (16.18%), although the differences with adenocarcinoma and nonsmokers were nonsignificant. Coexisting EGFR mutations were identified, and the incidence (8.54%) was similar to wild type (12.0%). High MET gene dosage was significantly associated with higher tumor stage (stage I + II versus stage III + IV; p = 0.0254) and prior chemotherapy for stage III + IV adenocarcinoma patients (35.71% versus 7.41%; p = 0.0145) but not correlated with primary TKI resistance. Among the 155 surgically resectable patients (stage I to IIIA), high MET gene dosage was significantly associated with shorter median survival (21.0 months versus 47.1 months; p = 0.042) by univariate analysis. Conclusions: High MET gene dosage was not related to primary TKI resistance and the incidence was increased after chemotherapy, suggesting high MET gene dosage may also be related to chemotherapy resistance.

Introduction The prognostic role of epidermal growth factor receptor ( EGFR ) mutations in patients with surgically resectable non-small cell lung cancer (NSCLC) without EGFR tyrosine kinase inhibitor treatment has not been well established, because the reports are still few. Materials and Methods We analyzed the survival data of 164 patients with surgically resectable (stages I to IIIA) NSCLC of two year groups (1996–1998 and 2002–2004), and compared with EGFR mutations, KRAS mutations, and EGFR gene copy numbers. Results Comparing the survival of wild-type patients and patients having L858R mutations or exon 19 deletion, the median survival was much longer for patient with EGFR mutations (54.7 months) than wild type (34.9 months). The difference was not statistically significant by univariate analysis ( p = 0.1981) but had borderline significance by multivariate analyses ( p = 0.0506). In addition, the 3-year survival rates of patients with EGFR mutations were also significantly higher than wild type ( p = 0.0232). After exclusion of 18 patients treated by EGFR-tyrosine kinase inhibitor for tumor recurrence, the trends were still the same. Patients with KRAS mutations had shorter median survival (21 months) than wild type (44.4 months). Patients with EGFR polysomy (≧copies) also had longer median survival (56.2 months) than wild type (53.4 months). But the survival differences of these two genetic markers were all not significant statistically. Conclusion It is intriguing that patients with NSCLC with EGFR mutations had better survival than wild type. Such a tumor biology may confound the survival data in a study without the stratification by EGFR mutation.

In the analysis of survival data, when nonproportional hazards are encountered, the Cox model is often extended to allow for a time-dependent effect by accommodating a varying coefficient. This extension, however, cannot resolve the nonproportionality caused by heterogeneity. In contrast, the heteroscedastic hazards regression (HHR) model is capable of modeling heterogeneity and thus can be applied when dealing with nonproportional hazards. In this paper, we study the application of the HHR model possibly equipped with varying coefficients. An LRR (logarithm of relative risk) plot is suggested when investigating the need to impose varying coefficients. Constancy and degeneration in the plot are used as diagnostic criteria. For the HHR model, a ‘piecewise effect’ (PE) analysis and an ‘average effect’ (AE) analysis are introduced. For the PE setting, we propose a score-type test for covariate-specific varying coefficients. The Stanford Heart Transplant data are analyzed for illustration. In the case of degeneration being destroyed by a polynomial covariate, piecewise constancy and/or monotonicity of the LRRs is considered as an alternative criterion based on the PE analysis. Finally, under the framework of the varying-coefficient HHR model, the meanings of the PE and AE analyses, along with their dynamic interpretation, are discussed.

Background/Purpose: Accurate length-of-stay (LOS) estimates have an impact on medical costs for stroke patients. Most studies have reported only descriptive sample means or have provided linear-model-based estimates for LOS. This study calculated point and interval estimates by treating hospital discharge as an event, and utilizing the proportional hazards (PH) model to provide the estimation of hospital stay for first-ever stroke patients in a rehabilitation department of a clinical center. Methods: Pairwise analysis for correlations between age, sex, comorbidity status, modified Barthel index (MBI) and functional independence measure (FIM) was performed. These explanatory variables are used in the K-sample comparisons, the χ 2 test for association, the PH regression analysis, and log-transformed linear (LTL) regression. Results: The PH model gave a prediction on estimated mean LOS, with an absolute bias of 0.85 days, by combining MBI and FIM into a single variable, or a bias of 1.15 days and 1.16 days with MBI and FIM vari- ables, respectively. The LTL-based estimation generated a bias of 5.91 days. The PH model has relatively shorter confidence intervals than those obtained by sample-mean and LTL methods. Conclusion: We recommend using the PH model for predicting mean LOS when the PH assumption for patients with different clinical characteristics is satisfied. However, the proposed method only applies to rehabilitating stroke patients. (J Formos Med Assoc 2009;108(8):653-662)

To explore the relationship of self-reported exposure to tobacco smoke and the cotinine levels in the urine and blood over the follow-up period for pregnant women. Three hundred ninety-eight pregnant women undergoing prenatal care were interviewed in different trimesters at three hospitals in central Taiwan using a structured questionnaire. Based on their self-reported smoking experience, the participants were classified into three groups (25 smokers, 191 passive smokers, and 182 non-smokers) and were tracked in this study up to the time of delivery. Cotinine levels were tested for the maternal blood and urine at the end of each trimester and for the umbilical cord-blood of the newborns. All specimens were measured using a sensitive high-performance liquid chromatographic (HPLC) technique. In general, urinary cotinine levels were higher in subjects who smoked (including current- and ex-smokers) than those who never smoked. The pattern of distribution of cotinine levels among smoking/ETS exposure group in the urine sample was similar to that in the blood sample. The umbilical cord-blood cotinine levels was found to be highest in the active smoking group, followed by the ETS group exposed to ETS both at home and in the workplace. Over the course of the pregnancies, there was an increase in cotinine levels in urine and maternal blood for each of 3 exposure groups. Exposure to smoking by self-reported information in pregnant women has been found to be directly related to the levels of cotinine in the umbilical cord-blood of the fetus. Cotinine is a sensitive measure of ETS exposure, but if biochemical analysis is not available or convenient for a pregnant woman, then self-reported exposure to ETS can provide a good estimate if the information is gathered by a well-trained interviewer in a structured way.

Dynamic or flexible regression models are used more and more often in carcinogenesis studies to relate lifetime distribution to time-depending explanatory variables. In addition to the classical regression models, such as the Cox model, AFT model, Linear transformation model, Frailty model, etc., we expose so-called flexible regression models, which are well adapted to study cross-effects of survival functions. Such effects are sometimes observed in clinical trials. Classical examples are well-known data concerning effects of chemotherapy (CH) and chemotherapy plus radiotherapy (CH + R) on survival times of gastric cancers patients. In this paper, we give examples which illustrate possible applications of the Hsieh model (2001) and the SCE model proposed by Bagdonavicius and Nikulin and adapted to treat survival data with one crossing point. We compare both models. Biblipgraphy: 40 titles.

In event time data analysis, comparisons between distributions are made by the logrank test. When the data appear to contain crossing hazards phenomena, nonparametric weighted logrank statistics are usually suggested to accommodate different-weighted functions to increase the power. However, the gain in power by imposing different weights has its limits since differences before and after the crossing point may balance each other out. In contrast to the weighted logrank tests, we propose a score-type statistic based on the semiparametric-, heteroscedastic-hazards regression model of Hsieh [2001. On heteroscedastic hazards regression models: theory and application. J. Roy. Statist. Soc. Ser. B 63, 63–79.], by which the nonproportionality is explicitly modeled. Our score test is based on estimating functions derived from partial likelihood under the heteroscedastic model considered herein. Simulation results show the benefit of modeling the heteroscedasticity and power of the proposed test to two classes of weighted logrank tests (including Fleming–Harrington's test and Moreau's locally most powerful test), a Renyi-type test, and the Breslow's test for acceleration. We also demonstrate the application of this test by analyzing actual data in clinical trials.

This paper presents results obtained for in vivo endogenous and exogenous 7-methylguanine (7-MG) analyzed using a method incorporating gas chromatography with electron-capture negative chemical ionization mass spectrometry and isotope dilution (GC/EC-ID-MS). 13C4-Labeled 7-MG was synthesized to serve as an internal standard to improve accuracy of quantitation, and was used to analyze 7-MG in livers of control mice and dacarbazine-treated mice. The results confirm that 7-MG in tissue DNA can be measured using this GC/EC-ID-MS method with excellent sensitivity and specificity. Administration of 0, 30, and 60 mg/kg dacarbazine to mice led to dose-dependent increases in the formation of 7-MG. The results indicate that this method could be applied to the analysis of endogenous and exogenous 7-MG in human tissues for future molecular epidemiology studies on potential health effects caused by methylating agents.

OBJECTIVES: To compare the practicality, reliability, validity, and responsiveness of the timed up and go (TUG), one-leg stand (OLS), functional reach (FR), and Tinetti balance (TB) performance measures in people aged 65 and older. DESIGN: A prospective study. SETTING: Shin-Sher Township of Taichung County, westcentral Taiwan. PARTICIPANTS: Twelve hundred community-dwelling older people. MEASUREMENTS: During an initial assessment at their residences, participants were interviewed for demographics, cognition, fall history, use of a walking aid, and activities of daily living (ADLs), in addition to completing the four balance tests. Falls were ascertained by telephone every 3 months for a 1-year follow-up; the four balance measures and ADLs were also reassessed at the end of the follow-up year. RESULTS: Of the four balance measures, the OLS had the lowest participation rate, and participation of people who were cognitively impaired had fallen in the previous year, used a walking aid, or suffered from an ADL disability was lower than for their counterparts. The time to complete the tests ranged from 58 seconds for OLS, to 160 seconds for the TB. All four balance measures exhibited excellent testretest reliability and discriminant validity but poor responsiveness to fall status. The TB showed better discriminant, convergent, and predictive validities and responsiveness to ADL changes than the other three tests. CONCLUSION: According to psychometric properties, the most suitable performance measure for evaluating balance in community-dwelling older people was the TB, followed by the TUG. J Am Geriatr Soc 52:1343–1348, 2004.

A 20-month prospective study was conducted to investigate the effect of motorcycle crash experience on changes in risk taking among 2514 urban and 2304 rural students in Taiwan. Risk taking was assessed using a 14-item self-administered questionnaire at the beginning and end of the study. A risk-taking score for each student at the initial and the last follow-up assessments was generated from adding up points across all 14 items. For exposure variables, the study documented past motorcycle crash history at the initial assessment and collected detailed information about any motorcycle crash involvement that occurred during the study period. A general linear mixed model was applied to assess the effects of prior and recent crash involvements on the path of risk-taking behavior. The results show that at the initial assessment, students with crash experience had higher risk-taking levels than those without crash experience. However, crash experience, irregardless of whether it was measured in terms of crash history prior to the study, crash frequency, time elapsed since the last crash, or crash severity, did not significantly change the risk-taking path among students, even though its effect differed between urban and rural areas.

A Cox-type regression model accommodating heteroscedasticity, with a power factor of the baseline cumulative hazard, is investigated for analyzing data with crossing hazards behavior. Since the approach of partial likelihood cannot eliminate the baseline hazard, an overidentified estimating equation (OEE) approach is introduced in the estimation procedure. Its by-product, a model checking statistic, is presented to test for the overall adequacy of the heteroscedastic model. Further, under the heteroscedastic model setting, we propose two statistics to test the proportional hazards assumption. Implementation of this model is illustrated in a data analysis of a cancer clinical trial.

Background: The time schedules for response evaluation of epidermal growth factor receptor-tyrosine kinase Inhibitor (EGFR-TKI) in non-small cell lung cancer (NSCLC) patients are still ill-defined. Methods: Stage IIIB/IV patients with histologically proven NSCLC were enrolled in this study if the tumor cells bore EGFR mutations other than T790M. Eligible patients were treated with either 250 mg of gefitinib or 150 mg of erlotinib once daily. The early response rate [computed tomography (CT) scan on Day 14], definitive response rate determined on Day 56, progression-free survival (PFS), overall survival (OS), and toxicity profile were assessed prospectively. Results: Thirty-nine patients were enrolled in this study. A total of 29 patients (29/39, 74.4%) achieved partial response (PR). Twenty-one patients (21/39, 53.8%) had early radiological response on Day 14. The early radiological response rate in patients with PR was 72.4% (21/29). Only eight patients without a PR on early CT still ended with PR. Among the 29 patients with PR, the PFS (8.1 months) and OS (18.3 months) of the 21 patients with early CT response were shorter than those of the 8 patients without early CT response (11.9 and 24.0 months for PFS and OS, respectively). But the survival differences were statistically non-significant. Conclusions: A very high percentage (72.4%, 21/29) of NSCLC patients with EGFR mutations with PR demonstrates early radiological response to EGFR-TKIs, which would advocate early radiological examination for EGFR-TKI therapy in NSCLC patients.

BACKGROUND & AIMS: The correlation between chronic hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) has been well-established. But the roles of viral factor remain uncertain. Only HBV X gene and nonsense mutations of S gene (C-terminal truncation of HBV surface protein) have been demonstrated to have transforming activity. Whether they play a significant role in hepatocarcinogenesis is still uncertain. METHODS: Twenty-five HBV-related HCC patients were positive for hepatitis B core antigen (HBcAg) in the cancerous parts of their HCC liver tissues by immunohistochemistry studies, and had available tissue for whole HBV genome sequence analysis. The results were compared with 25 gender and age-matched HBcAg negative HCCs. Plasmids encoding HBV S gene nonsense mutations identified from HBcAg (+) HCC tissue were constructed to investigate their cell proliferation, transformation activity and the oncogenic potentials by xenograft study and in vivo migration assay. RESULTS: HBcAg (+) HCC patients were significantly associated with cirrhosis and small tumor size (≦2 cm) when compared with HBcAg (-) HCC patients. Southern blot analyses revealed freely replicative forms of HBV in the cancerous parts of HBcAg(+) HCC. Three nonsense mutations of S gene (sL95*, sW182*, and sL216*) were identified in the HBcAg(+) HCC tumor tissues. sW182* and sL216* were recurrently found in the 25 HBcAg (-) HCC tumor tissue, too. Functional studies of the above 3 non-sense mutations all demonstrated higher cell proliferation activities and transformation abilities than wild type S, especially sW182*. Tumorigenicity analysis by xenograft experiments and in vitro migration assay showed potent oncogenic activity of sW182* mutant. CONCLUSIONS: This study has demonstrated potent oncogenic activity of nonsense mutations of HBV S gene, suggesting they may play an important role in hepatocarcinogenesis.

Globally, influenza infection is a major cause of morbidity and mortality in the elderly, who are suggested to be the major target group for trivalent influenza vaccine (TIV) vaccination by World Health Organization. In spite of an increasing trend in vaccine coverage rates in many countries, the effect of vaccination among the elderly in reducing hospitalization and mortality remains controversial. In this study, we conducted a historical cohort study to evaluate the temporal pattern of influenza-associated morbidity among persons older than 64 years over a decade. The temporal patterns of influenza-associated morbidity rates among the elderly older than 64 years indicated that Taiwan's elderly P&I outpatient visits have been decreasing since the beginning of the 1999–2000 influenza season; however, hospitalization has been increasing despite significant increases in vaccine coverage. The propensity score logistic regression model was implemented to evaluate the source of bias and it was found that the TIV-receiving group had a higher propensity score than the non-receiving group (P

BACKGROUND: Population studies on trends of varicella and herpes zoster (HZ) associated with varicella zoster vaccination and climate is limited. METHODS: This study used insurance claims data to investigate the chronological changes in incident varicella and HZ associated with varicella zoster vaccination. Poisson regression was used to estimate the occurrence of varicella associated with the occurrence of HZ and vice versa by year, season, sex, temperature, and sunny hours. RESULTS: The varicella incidence declined from 7.14 to 0.76 per 1,000 person-years in 2000-2009, whereas the HZ incidence increased from 4.04 to 6.24 per 1,000 person-years. Females tended to have a higher risk than men for HZ (p

Hepatocellular carcinoma (HCC) is the leading cancer death in Taiwan. Chronic viral hepatitis infections have long been considered as the most important risk factors for HCC in Taiwan. The previously published reports were either carried out by individual investigators with small patient numbers or by large endemic studies with limited viral marker data. Through collaboration with 5 medical centers across Taiwan, Taiwan liver cancer network (TLCN) was established in 2005. All participating centers followed a standard protocol to recruit liver cancer patients along with their biosamples and clinical data. In addition, detailed viral marker analysis for hepatitis B virus (HBV) and hepatitis C virus (HCV) were also performed. This study included 3843 HCC patients with available blood samples in TLCN (recruited from November 2005 to April 2011). There were 2153 (56.02%) patients associated with HBV (HBV group); 969 (25.21%) with HCV (HCV group); 310 (8.07%) with both HBV and HCV (HBV+HCV group); and 411 (10.69%) were negative for both HBV and HCV (non-B non-C group). Two hundred two of the 2463 HBV patients (8.20%) were HBsAg(-), but HBV DNA (+). The age, gender, cirrhosis, viral titers, and viral genotypes were all significantly different between the above 4 groups of patients. The median age of the HBV group was the youngest, and the cirrhotic rate was lowest in the non-B non-C group (only 25%). This is the largest detailed viral hepatitis marker study for HCC patients in the English literatures. Our study provided novel data on the interaction of HBV and HCV in the HCC patients and also confirmed that the HCC database of TLCN is highly representative for Taiwan and an important resource for HCC research.

Background It is well known that familial sick sinus syndrome (SSS) is caused by functional alterations of ion channels and gap junction. Limited information is available on the mechanism of age-related non-familial SSS. Although evidence shows a close link between arrhythmia and the renin-angiotensin system (RAS), it remains to be determined whether the RAS is involved in the pathogenesis of non-familial SSS. Methods In this study, 113 patients with documented non-familial SSS and 125 controls were screened for angiotensinogen (AGT) and gap junction protein-connexin 40 (Cx40) promoter polymorphisms by gene sequencing, followed by an association study. A luciferase assay was used to determine the transcriptional activity of the promoter polymorphism. The interaction between nuclear factors and the promoter polymorphism was characterized by an electrophoretic mobility shift assay (EMSA). Results Association study showed the Cx40 -44/+71 polymorphisms are not associated with non-familial SSS; however, it indicated that four polymorphic sites at positions -6, -20, -152, and -217 in the AGT promoter are linked to non-familial SSS. Compared to controls, SSS patients had a lower frequency of the G-6A AA genotype (OR 2.88, 95% CI 1.58–5.22, P = 0.001) and a higher frequency of the G allele at -6 position (OR 2.65, 95% CI 1.54–4.57, P = 0.0003). EMSA and luciferase assays confirmed that nucleotide G at position -6 modulates the binding affinity with nuclear factors and yields a lower transcriptional activity than nucleotide A (P

To examine the rate of early HBeAg loss and predictors of HBeAg loss in HBeAg-positive chronic hepatitis B (CHB) patients with acute exacerbation (AE) treated with lamivudine.A total of 146 patients diagnosed with CHB and AEs were included in this retrospective study. Patients were divided into two groups: decompensated and compensated.The mean treatment duration for the decompensated and compensated groups was 18.1 and 19.9 months, respectively. Decompensated patients were significantly older and had a higher prevalence of cirrhosis and genotype B infection than compensated patients. Compared to compensated patients, decompensated patients achieved a higher rate of HBeAg loss (25.8 vs. 14.3%; P = 0.0805) at 3 months of therapy, a higher rate of serum HBV DNA negativity (53.2 vs. 29.8%; P = 0.0042), and a lower rate of rtM204V/I mutation (3.2 vs. 16.7%; P = 0.0139) after 12 months of lamivudine therapy. The rates of HBeAg loss after 6 and 12 months of lamivudine therapy were similar between the two groups. Logistic regression analysis revealed that female gender and baseline ALT level ≥1,000 IU/L, but not decompensations, were significant predictors of HBeAg loss at 3 months; however, only female gender was a significant predictor of HBeAg loss after 6 and 12 months of lamivudine therapy. The early HBeAg losers showed a significantly higher sustained remission rate off lamivudine therapy.Female gender and baseline serum ALT level ≥1,000 IU/L were independent predictors of early HBeAg loss during lamivudine therapy in HBeAg-positive CHB patients with AE.The online version of this article (doi:10.1007/s12072-010-9227-x) contains supplementary material, which is available to authorized users.

Background: Prolonged surgical workload and different starting times of laparoscopic-assisted vaginal hysterectomy (LAVH) might be factors influencing surgical and patient's outcomes. Aims: The aim of this study is to elucidate possible detrimental results of the schedule effect on LAVH. Methods: Retrospective cohort study based on patient charts and hospital's electronic database in a tertiary teaching hospital. A total of 217 consecutive women who underwent LAVH for gynecological diseases were enrolled. Among them, 159 LAVHs performed by four surgeons were divided into three groups according to three different starting times of the operation. Among 159 LAVHs, 110 performed by the same surgeon were divided into three groups in the same way. Variables related to operative and medical outcomes were compared and analysed by one-way anova and chi-squared test. Results: Data on both all women (159 cases) and subgroup women (110 cases) revealed that no statistical significant differences among the three groups including length of hospital stay, shift of serum haemoglobin, shift of serum haematocrit, flatulence-relief time, surgical blood loss, blood transfusion rate, rate of postoperative fluid injection over two days after surgery or complication rate. Interestingly, the first LAVH scheduled within the 08.30 to 10.29 hours time slot had the longest mean operation time. LAVHs starting within the 15.30 to 17.29 hours time slot had the shortest mean operation time. Conclusion: The time of day in which LAVH is performed does not have a detrimental effect on outcome. Successful LAVH is dependent on multidisciplinary team work to achieve good surgical and patient outcomes.

⋄ Objectives Comparisons of survival in patients on peritoneal dialysis (PD) and on hemodialysis (HD) have been conducted in many Western countries, but publications on this subject in Asian populations are scarce. The present study estimated the survival and the relative mortality hazard for HD and PD patients in Taiwan. ⋄ Methods Incident end-stage renal disease patients reported to the Taiwan Renal Registry during 1995 – 2002 were included in the study. Patients had to be 20 years of age or older and had to have survived for the first 90 days on dialysis. A total of 45 820 incident HD and 2809 incident PD patients formed the study population. Patients on PD were treated mainly with traditional glucose-based solutions. Using an intent-to-treat analysis, the Cox proportional hazards (CPH) model was applied to identify the factors that predict survival by treatment modality. Subgroup analyses were conducted by stratifying patients according to sex, comorbidity, age, and diabetes status. Kaplan–Meier estimates were used to explore the survival of HD and PD patients. Adjustments were implemented using the CPH model. ⋄ Results The overall 1-year, 2-year, 3-year, 5-year and 10-year survival rates for PD patients were 89.8%, 77.6%, 67.6%, 55.5%, and 35% respectively. The equivalent survival rates for HD patients were 87.5%, 76.6%, 68.1%, 54.3%, and 33.8%. The differences were not statistically significant ( p = 0.125). The CPH analysis stratified by diabetes status and age revealed that PD patients 55 years of age or younger and nondiabetic had a lower mortality ratio (MR) of 0.94. But the MR increased to 1.31 for nondiabetic patients older than 55. The MR for PD versus HD further increased to 1.72 for diabetic patients 55 years of age or younger, and to 1.99 for diabetic patients older than 55. ⋄ Conclusions After adjusting for both demographic and clinical case-mix differences, PD and HD patients were observed to have similar long-term survival. Subgroup analyses revealed that, among diabetic patients and patients older than 55, those on HD experienced better survival than did those on PD.

This study investigated whether mothers with prenatal environmental tobacco smoke (ETS) exposure increased the newborn genetic damage and adverse birth outcomes. Study participants were women receiving prenatal care at three hospitals in Central Taiwan and their newborns. Participants were divided into two groups (nonsmokers and ETS-exposed non-smokers) based on maternal ETS-exposed status. Comet assay were performed for cord blood samples. Infants born to mothers with prenatal ETS exposure had the highest mean cord blood DNA damage score (69.7 +/- 42.3) and poorer birth outcomes. No negative fetal growth effects appeared among newborns with low DNA damage levels. Among newborns with high DNA damage levels (comet scores >50), those born to prenatal ETS exposure had an average reduction of 252.7 g in birth weight, 1.10 cm shorter in length and a 0.92-cm decrease in head circumference, compared to newborns with no smoking exposure. This study shows that the DNA damage scores can be used as an effect-modifier on the relationships between ETS exposure and adverse birth outcome. The association appears more apparent for the ETS exposure in relation with more severe DNA damage.

We consider a piecewise-constant varying-coefficient model to account for survival data with multiple crossings. Estimating procedures are provided, and a class of tests is constructed in order to impose varying coefficients for some specific covariates, or for some other purposes. Analysis of the survival of Taiwan’s stroke patients is reported to illustrate the applications.

Objective We analyzed data from the National Health Insurance Research (NHIR) database in the year 2000 to estimate the seasonal variation in the chickenpox rate in Taiwan. Patients and Methods All chickenpox cases listed in the NHIR database were included ( n = 165,719). A Lorenz curve was plotted and a chi-square test for equal proportions calculated for seasonal variation. To determine the effects of temperature and season on outcome values, generalized estimating equation methods were utilized to adjust the effects of other possible influencing factors and take into account the within-subject dependence over repeated assessments. Results All four regions of the country had highest incidence rates in January, and three of them had lowest rates in September. Incidence was significantly higher in females aged 15‐24 years than in males. An increment of 1 ° C resulted in an incidence ratio of approximately 0.98 or, equivalently, a 10 ° C increment gives an incidence ratio of approximately 0.78. Conclusion The results suggest that season and temperature are significantly related to the incidence of chickenpox. Infectious diseases can be monitored. Prevention procedures can be taken by understanding its pattern and activity in order to decide the best policy for vaccination. Further studies are warranted, particularly for long-term trends, and in other nations with different seasonal temperatures from Taiwan.